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Development of the Kidney in Mouse and Human | ATLAS-D2K Center

Development of the Kidney in Mouse and Human

Provided by Andrew McMahon, University of Southern California
October 2017 (GUDMAP)

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The functional unit of the kidney is the nephron. Molecular, cellular and genetic studies (reviewed in McMahon 2016) have provided important insights into how nephron progenitors within the cap mesenchyme of the mouse kidney enter a nephron forming pathway, and subsequent steps in the morphogenesis and patterning of nephron precursors to generate mature nephron structures.

Diagram of the developing kidney
From: McMahon AP. (2016) Development of the Mammalian Kidney. Curr Top Dev Biol. 117:31-64. PMID: 26969971

Dynamic events in nephrogenesis

Kidney development is dynamic. Normal development requires the coordination of interactions among multiple cell types over an extensive developmental period for the formation, organization and function of the kidney. How can we obtain a dynamic view of developmental processes that normally take place with the fetus? Kidney organ cultures with genetically marked strains of mice - as in the video below - open the door to understanding developmental events in space and time.

Mouse versus the human kidney

In human kidney development, there are distinct differences in the timing, output and overall structure that is formed compared to the mouse kidney. What underlies the species specific differences and how can we develop a much improved understanding of how our own kidney’s form?

Comparing mouse and human kidneys
Comparing mouse and human kidney

Modeling human kidney development

Through a molecular and cellular analysis of nephron formation in the developing human kidney (left panel), we can build models of nephron-forming processes (middle panel). These will inform efforts to generate dynamic developmental models of human kidney formation from pluripotent stem cells (PSC; right panel: PSC-derived human kidney organoid)

Nephron Patterning In The Human Kidney
Nephron Patterning In The Human Kidney
Comparing mouse and human kidnes
Nephron Precursor From The Human Kidney
Nephrons Forming  In A Human Kidney Organoid Model System
Nephrons Forming In A Human Kidney Organoid Model System